tbuckley/cabot-search huggingface dataset:
Abstract 15001: Correlating Site of Origin in Ventricular Arrhythmias With Site of Inflammation in Patients With Underlying Myocardial Inflammation via FDG-PET Scan
Authors: Rishi Charate, Adnan Ahmed, Naga Pothineni, Rakesh Gopinathannair, Dhanunjaya Lakkireddy
Journal: Circulation (2022)

Introduction: Patients with underlying myocardial inflammation often present with otherwise unexplained ventricular arrhythmias. We seek to further elucidate if these arrhythmias originate from the areas of inflammatory FDG uptake, suggesting a direct arrhythmogenic substrate. Hypothesis: To determine if sites of inflammation on Fluorodeoxyglucose (FDG)-PET scan correlate with the site of origin on electroanatomic mapping for PVC/VT ablation in underlying myocardial inflammation. Methods: We retrospectively reviewed patients presenting with frequent ventricular arrhythmias (PVC/VT) with positive FDG-PET scans indicative of underlying myocardial inflammation, and included patients who had persisting, symptomatic, burdensome arrhythmias despite multiple cycles of immunosuppressive therapy or resolution of inflammation that eventually required catheter ablation for PVC/VT. Patients were then reviewed to see if their site of origin (SOO) of PVCs or VT correlated with the site of inflammation (SOI) seen on FDG-PET scan. Results: We studied 42 patients with documented PVCs or VT, a positive FDG-PET scan and eventual PVC/VT ablation. Mean age was 58.9 years + 14.5. Mean EF was 42.6 + 8.6%. Average PET SUV Max was 3.8 + 1.2, with an average involvement of 2.7 + 2.1 segments. Nearly all patients had multiple sites of FDG uptake (95.2%), with 69.% localized vs 31.0% diffuse distributions. The 42 patients had SOO in the following distribution: RVOT (30.1%), Inferoseptal (26.2%), RCC area, (19.0%), LVOT: (14.3%), Anteroseptal: (14.3%), Basal (11.9%), LV Summit (9.5%), and anterolateral (4%). 35.7% of patients had multiple SOO. Exact correlation between SOO-SOI was seen in 23/42 (54.8%), whereas partial correlation (matching sites with additional PVC locations vs uptake distributions, or additional uptake distributions vs PVC locations) was seen in 10/42 (23.8%). No correlation was seen in 9/42 (21.4%). Of the 19 that had partial or no correlation, the most frequent distributive area of uptake without PVC correlation was anterolateral, present in 7/19 (36.8%). Conclusions: In our retrospective study, patients undergoing cardiac FDG-PET scans to confirm myocarditis, had a positive correlation of site of PVC/VT origin and site of inflammation.
Abstract 15077: Reconnection of Pulmonary Veins and Left Atrial Posterior Wall Following Catheter Ablation for Atrial Fibrillation in Real-World Patients: Registry Data From a High-Volume Center
Authors: Sanghamitra Mohanty, Sai Shishir Shetty, Karim Baho, Issa Asfour, Domenico G Della Rocca, ANGEL QUINTERO MAYEDO, Bryan MacDonald, Carola Gianni, Trevor Morris, Danielle Kessler, Mohamed Bassiouny, G Gallinghouse, John Burkhardt, Rodney Horton, Amin Al-Ahmad, Luigi Di Biase, Luigi Di Biase, Andrea Natale
Journal: Circulation (2022)

Introduction: Durable isolation of the pulmonary veins (PV) and the left atrial posterior wall (LAPW) are considered as key determinants of long-term success after catheter ablation in AF patients. Objective: We aimed to evaluate the PV and LAPW reconnection rate in real-world patients undergoing redo-ablation at our center. Methods: Consecutive AF patients that underwent their first AF ablation at our center from 2015-19 were included in this analysis. At the index procedure, all received electrical isolation of PVs and the LAPW area between the PVs, using radiofrequency (RF) ablation. Procedure was conducted with 3.5-mm irrigated-tip catheter guided by circular mapping catheter, intra-cardiac echocardiography and a 3-D mapping system. RF energy was delivered with a maximum temperature setting of 42 0 C, contact force of 10g and a power of up to 45W. Posterior wall isolation was performed using multiple ablation points covering the whole posterior wall. An esophageal probe was utilized in all patients to monitor esophageal temperature during ablation in the LAPW in close proximity to the esophagus. Complete abolition of all PV potentials rather than decrease in the amplitudes was the end point and confirmed by entrance and/or exit block. All patients were followed up prospectively for 2 years with quarterly evaluation during the first year and bi-annually afterwards and the data was collected in our IRB-approved AF registry. Recovery of conduction in the PVs and LAPW were assessed at the redo procedure using pacing or incremental isoproterenol infusion of 20- 30μg/min for 15-20min. Results: During the study period, 6,817 AF ablation procedures were performed at our institution of which 3,113 AF patients undergoing their first catheter ablation were included in the analysis and prospectively followed up for 2 years. Baseline characteristics of the study population is given in Table 1. At 23.1±12.8 months of follow-up, 614 (19.7%) patients had received redo-ablation, of which 139 (22.6%) had one or more PV or LAPW reconnected. Conclusion: In this series, with experienced operators performing the procedures, the rate of recovery of conduction in the PVs and LAPW was low compared to the reported high incidence rate in the literature.
Abstract 15040: Atrial Arrhythmia Burden and Mortality in Patients With Congenitally Corrected Transposition of The Great Arteries (ccTGA)
Authors: Anca Chiriac, Bhalla Jaideep, Samantha Espinosa, Goyal Umadat, Carolyn Gonzalez, Sabrina D Phillips, Samuel Asirvatham, Malini Madhavan, Christopher J McLeod
Journal: Circulation (2022)

Background: Patients with ccTGA have a high incidence of atrial arrhythmias and premature failure of the systemic right ventricle. We sought to better define this risk. Methods: A retrospective review of all clinical data for patients with ccTGA followed at a large tertiary care institution was performed. The primary outcome was a composite of death and cardiac transplantation. Results: A cohort of 165 patients (age 41±16 years, 53% male) were followed for 11±8 years; 41 patients died, 7 underwent cardiac transplantation, and 4 underwent VAD placement. Male sex (HR 2.7, p=0.002), older age (HR 1.04, p&lt;0.001), clinical heart failure symptoms (HR 7, p&lt;0.001), heart failure hospitalization (HR 4.9, p&lt;0.001), syncope (HR 1.8, p=0.04) and pulmonary hypertension (HR 2.77, p&lt;0.001) were significant predictors of the primary outcome. Atrial fibrillation (HR 3.5, p=0.002), atrial flutter (HR 3.05, p=0.04), and prolonged QRS duration (HR 1.01, p=0.004) on the first ECG, as well as right and left atrial enlargement (HR 4, p&lt;0.001 and 3.7, p&lt;0.003) and severe systemic AV valve regurgitation (HR 3.8, p=0.03) on the first echocardiogram were associated with poor outcomes. Atrial arrhythmias occurred in 110(67%) patients: atrial fibrillation in 75(45%), atrial flutter in 50(30%), and supraventricular tachycardia in 16(9.7%) patients. Arrhythmias were largely asymptomatic in 109(66%) patients, while 25(14.5%) experienced palpitations, dizziness or presyncope, and 10(6%) presented with decompensated heart failure. Cardioversion and antiarrhythmic therapy were utilized in 53(32%) patients. Surgical pulmonary vein isolation or atrial MAZE were performed in 15(9%) patients, cryoablation of the CTI in 3 patients, and surgical ablation of an accessory pathway in 2 patients. One or more catheter ablation procedures were also performed in 18(11%) patients. Conclusions: Atrial fibrillation and flutter, heart failure, prolonged QRS duration, systemic AV valve regurgitation and pulmonary hypertension predict worse outcomes in ccTGA. Although asymptomatic in a majority of patients, atrial arrhythmias are associated with significant morbidity and mortality. Whether a rhythm control strategy even in asymptomatic patients may improve outcomes remains unknown.
Abstract 15069: The Rna M <sup>6</sup> A Demethylase, Fto, Regulates Vascular Remodeling in the Pathogenesis of Pulmonary Arterial Hypertension
Authors: Jingbo Dai, Yi Peng, Maggie M Zhu, Youyang Zhao
Journal: Circulation (2022)

Introduction: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by obliterative pulmonary vascular remodeling and progressive elevation of pulmonary vascular resistance that leads to right heart failure and premature death. RNA modifications such as N6-methyladenosine (m 6 A) has have recently been discovered as essential regulators of gene expression but its function in regulating the development of PAH remain unclear. Hypothesis: Fat mass and obesity-associated protein (FTO), as a major m 6 A eraser, acts as a key regulator of endothelial cell (EC) dysfunction and pulmonary vascular remodeling and, thus, is a novel therapeutic target for PAH. Methods: To determine the FTO expression on the idiopathic PAH (IPAH) patients, we performed Western blotting and immunofluorescence on lung tissue from IPAH patients. A novel mouse model with Tie2-Cre-mediated deletion of Fto in endothelial cells was generated and treated with hypoxia for 3 weeks to induce experimental PAH. Measurement of right ventricular systolic pressure (RVSP) and weight ratio of right ventricular versus left ventricular plus septum (RV/LV+S), an indicator of RV hypertrophy were determined. To evaluate the translational potential of targeting FTO in PAH, rats were exposed to monocrotaline to induce pulmonary hypertension and then were treated with FTO inhibitor FB23-2. RVSP, RV/(LV+S) ratio and histology assessment were measured subsequently. Results: FTO expression level is markedly elevated in the endothelial cells of IPAH patients. The Tie2-Cre-Fto (CKO) mice exhibited inhibited PAH under hypoxia treatment as evident by reduced RVSP and lower RV/(LV+S) ratio. Histological and immunofluorescent staining showed that media layer of pulmonary arteries had less cell proliferation and reduced pulmonary vascular remodeling. Moreover, preclinical MCT-rat PAH model showed attenuated PAH phenotype as well as pulmonary vascular remodeling with pharmacological inhibition of FTO. Conclusions: These studies demonstrate that FTO expression markedly elevates in the EC of IPAH patients. Tie2-Cre mediated loss of FTO protects mice from hypoxia-induced PAH. Thus, targeting FTO is a promising therapeutic strategy for PAH.
Abstract 15067: Stress Hyperglycemia on Hospital Admission Drives the Risk of Re-Hospitalization for Chest Pain in INOCA Patients
Authors: Pasquale Mone, Xujun Wang, Luigi Salemme, Angelo Cioppa, Grigore Popusoi, Antonella Pansini, Tullio Tesorio, Gaetano Santulli
Journal: Circulation (2022)

Introduction: Ischemia with non-obstructive coronary arteries (INOCA) is a relatively new condition, often observed in patients with angina. However, the exact pathophysiology of INOCA is not fully understood, and its management remains very debated. Hypothesis: We hypothesized that admission hyperglycemia in INOCA patients could be associated with the risk of being re-hospitalized for chest pain. Methods: We evaluated INOCA patients referred to our Institution between 2016 and 2021 for percutaneous coronary intervention (PCI). We divided our population in quintiles according to the values of the stress hyperglycemia ratio (SHR), calculated as the ratio of admission blood glucose (expressed as mmol/L) and HB1Ac (%). We calculated Kaplan-Meier product limits for cumulative ratio of reaching the endpoint and we applied the log-rank test. To further confirm our results, we performed a multivariable analysis in order to adjust for potential confounders. Results: 2874 INOCA patients were enrolled in our study. At 1-year follow-up, the risk of hospitalization for chest pain was progressively higher in patients with higher SHR values (p&lt;0.001). To rule out the impact of potential confounders, we performed a multivariable analysis adjusting for potential risk factors for re-hospitalization, including age, BMI, hypertension, dyslipidemia, diabetes, smoking, and creatinine; this analysis confirmed the significant association of admission SHR and re-hospitalization in INOCA patients. Conclusions: To the best of our knowledge, this is the first report showing that admission SHR is an independent risk factor for hospitalization in INOCA patients, with or without diabetes. Our data indicate that hyperglycemia may trigger coronary microvascular dysfunction driving worse outcomes in this class of patients; in this context, glycemic control may be a main goal to be achieved in this population. Further studies in larger populations and with a longer follow-up are warranted to confirm our findings.
Abstract 15056: Cardiac P62/sqstm1 Deficiency Exacerbates Hypoxic Stress vi <i>a</i> Impaired Hypoxia Inducible Factor 1α Signaling
Authors: Rajeshwary Ghosh, Nima Fatahian, Marissa Hathaway, Sophie Stephens, Siu-Lai Desmond Chung, Isaac D Cao, John D Symons, Sihem Boudina
Journal: Circulation (2022)

Ischemic heart disease (IHD), a major cause of heart failure, is characterized by metabolic dysfunction and myocardial cell death. Cellular hypoxia activates hypoxia inducible factor 1α (HIF1α) to initiate metabolic, angiogenic, and growth-factor related responses. Under normoxia, HIF1α is degraded by prolyl hydroxylase (PHD) domain-containing proteins via the proteasome. Due to the short half-life of HIF1α (&lt;5mins), PHD inhibitors are utilized to stabilize HIF1α and improve cardiac function in pre-clinical models of ischemia/infarction. However, evidence exists that PHD inhibitors exert off-target effects. Based on prior studies in cancer cells demonstrating that the autophagy adaptor protein p62 prevents HIF1α degradation, we hypothesized that p62 stabilizes cardiac HIF1α and provides cardioprotection from hypoxia. We generated mice with tamoxifen-inducible cardiomyocyte-specific p62 deletion (p62icKO mice; 8 week male and female) and exposed them to 7% O 2 for 6h. Hypoxia increased cardiac mRNA expression of Sqstm1 , Bnip3 , and Hmox1 in wild-type (WT) but not p62icKO mice. Underscoring functional relevance, ejection fraction and fractional shortening were less, oxidative stress was elevated, and apoptosis was greater, in p62icKO vs. WT mice exposed to hypoxia. Mechanisms were evaluated using cultured H9c2 cardiomyoblasts exposed to 21% (normoxia) or 1% (hypoxia) O 2 for 24h. Hypoxia increased both HIF1α and p62 protein expression. To determine the role of p62, H9c2 cells were transfected with p62 or scrambled (ctrl) siRNA for 48h, followed by 24 h hypoxia. Hypoxia-induced HIF1α protein accrual and expression of HIF1α downstream targets Egln1 , Vegfa , Bnip3 and Hmox1 mRNA was attenuated in H9c2 cells transfected with p62 vs. control siRNA. These data indicate p62 stabilizes cardiac HIF1α and regulates its transcriptional activation. Thus, p62 could be a novel therapeutic target for treatment of IHD.
Abstract 15226: Association of Estimated Pulse Wave Velocity to Mortality in Heart Failure With Reduced Ejection Fraction. Insights From the HF-Action Trial
Authors: Sula Mazimba, Rebecca Woodhouse, Tolu P Oyinloye, Josephine Lamp, Nicholas Ashur, David Shisler, Lauren Taylor, Mohammad Abuannadi, Steven Phillips, Sami Ibrahim, John A Hossack, Nishaki M Mehta, Khadijah Breathett, Akua Boadu, James Bergin, Younghoon Kwon, Kenneth C Bilchick
Journal: Circulation (2022)

Introduction: Ventriculo-arterial coupling dynamics influence outcomes in heart failure (HF). Arterial stiffness (AS) is a key determinant of vascular load on the heart. We hypothesized that estimated pulse wave velocity (ePWV) would be associated with mortality. Methods: We analyzed the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) database for the association of ePWV with survival. ePWV was calculated using mean blood pressure (MBP) and Age using the equation: 9.587 – 0.402 х age + 4.560 х 10 –3 х age 2 – 2.621 х 10 –5 х age 2 х MBP + 3.176 х 10 –3 х age х MBP – 1.832 х 10 –2 х MBP. MBP was calculated as diastolic BP (DBP) + 0.4(SBP – DBP). Kaplan-Meier survival curves and Cox proportional hazards regression were used for analysis. Results: Among 768 patients (age 58.0 +/- 12.8 years, 31.8 % female), the median ePWV was 8.5 (IQR 7.2 to 10.2). There was a moderate correlation between ePWV and peak VO2 (r=-0.20, p&lt;0.0001) and between ePWV and the six-minute walk duration (r=-0.20, p&lt;0.0001). The unadjusted HR for ePWV and all-cause mortality was 1.15 per unit increase (95% CI 1.05-125). The unadjusted HRs for ePWV component covariates of age and MBP with all-cause mortality were 1.03 per year (95% CI 1.02-1.05, p &lt; 0.0001) and 0.985 per mm Hg (95% CI 0.971-1.000, p=0.053), respectively. With adjustment by peak VO2 above or below the median in a multivariable model, increasing ePWV was still associated with a greater probability of all-cause mortality (HR 1.11 per unit increase, 95% CI 1.01-1.21, p=0.02). In the model with adjustment by the six-minute walk duration, risk associated with ePWV was similar (HR 1.09, 95% CI 0.998-1.120, p=0.056). Kaplan-Meier curves also demonstrated an increased risk for ePWV greater than the median value of 8.5 (Figure). Conclusion: ePWV is associated with all-cause mortality in stable HF patients. More studies are needed to assess the utility of ePWV as a therapeutic target in HF.
Abstract 14731: Form and Function: 4D Flow Derived Hemodynamic Parameters in the Ascending Aorta is Reflective of Transverse Aortic Arch Dilation in Patients With Single Ventricle Physiology
Authors: Reena M Ghosh, Mohammed Elbaz, Thara Nallamothu, Andrea Jones, Jack Rychik, Matthew A Harris, Sara Partington, David Biko, Kevin Whitehead, Mark A Fogel
Journal: Circulation (2022)

Introduction: Reconstructed aortas in patients with single ventricle (SV) can dilate progressively over time, possibly due to abnormal flow patterns. Four-dimensional (4D) flow cardiac magnetic resonance imaging (CMR) can assess advanced hemodynamic parameters. This study utilizes 4D flow CMR to assess the association between ascending aorta (AAo) 4D flow dynamics of vorticity, viscous energy loss (EL) and kinetic energy (KE) with arch anatomy in SV patients. Methods: This was a retrospective single center study of all patients with SV who underwent 4D flow CMR from June 2021-present. Vorticity, KE and EL were calculated over the segmented three-dimensional AAo, and values were normalized to cardiac index (CI). Cross-sectional areas of the aortic root, AAo and transverse aorta were indexed to body surface area. Linear regression was used to determine associations between hemodynamic parameters and arch anatomy. Results: 20 pts met inclusion criteria; 5 were excluded due to incomplete datasets. The remaining 15 pts had a median age of 57 months (IQR 31;117.5). Ten (66%) had a systemic RV, 13 (86%) had a reconstructed aorta and 40% were after the Fontan operation. Peak and mean vorticity in the AAo were positively associated with transverse arch area. Additionally, there was a positive association between both total EL and EL index, and transverse arch area. (see table) Conclusions: Higher vorticity and EL in the AAo are associated with and reflective of higher transverse arch areas (i.e. dilation) in SV pts. In depth research in a prospective, longitudinal cohort is warranted to better understand this relationship and the geometry relative to hemodynamics. Furthermore, correlation of 4D flow metrics with clinical outcomes may provide novel insights into modifiable risk factors in this patient population
Abstract 15144: Bmp10 is a Novel Marker of Rhythm Status in Atrial Fibrillation
Authors: Miles Barney, Dawood Darbar
Journal: Circulation (2022)

Background: Atrial fibrillation (AF), the most common cardiac arrhythmia requiring therapy, is associated with significant morbidity and increased mortality. A major challenge in assessing disease progression and efficacy of AF therapy is the rigor of AF identification and, despite a critical need, there is no effective biomarker that tracks burden of disease or response to therapy. BMP10, a critical signaling molecule during cardiac development, has emerged as a promising marker for response to catheter ablation, however it is unknown whether BMP10 tracks AF burden. To evaluate BMP10 as a potential biomarker for AF burden, I sought to determine whether plasma levels of BMP10 could track rhythm status. Methods: 40 patients with an active history of AF were prospectively enrolled in a clinical biorepository and plasma samples were collected at the time of enrollment. Rhythm status at enrollment was determined by ECG. Plasma BMP10 levels were measured by ELISA (LSBio). Results: Of the 40 patients enrolled, 23 were in sinus rhythm (SR) and 17 were in an episode of AF. Baseline characteristics were similar across the two groups (Table 1). Patients who were in an active AF episode had higher levels of plasma BMP10 (1.94 ng/mL, SEM: 0.19) than patients in SR (1.44 ng/mL, SEM 0.11) (p= 0.04). (Figure 1) CONCLUSION: Blood plasma BMP10 is modulated by rhythm status in patients with AF, suggesting that BMP10 may be a promising biomarker for AF burden and response to therapy. Table 1. Baseline Characteristics of Rhythm Status Groups Figure 1. Plasma BMP10 Levels by Rhythm Status
Abstract 14496: NOX2 Inhibition Reverses Atrial Remodeling Caused by Increased Oxidative Stress and Reduces AF in Diet Induced Obese Mice
Authors: Arvind Sridhar, Mahmud Arif Pavel, Olivia T Ly, Hanna Chen, Miles Barney, Francisco Gonzalez, Srikanth Perike, Mark McCauley, Jalees Rehman, Dawood Darbar
Journal: Circulation (2022)

Introduction: Diet induced obese (DIO) mice display increased inducible atrial fibrillation (AF) and an overall increase in reactive oxygen species (ROS) production. NADPH oxidase 2 (NOX2), a major source of cytosolic ROS production in human atria, has been implicated in AF independent of obesity and is significantly increased in the atria of DIO mice. Although treatment with MitoTEMPO, a mitochondrial specific antioxidant reduced AF burden in DIO mice, the actual role of NOX2 in increasing ROS production and atrial remodeling in the context of obesity-induced AF remains unclear. Hypothesis: To test the hypothesis that increased NOX2 modulates atrial remodeling in obesity-induced AF, we used control mice, DIO and Nox2 -KO mice fed with a 60% HFD for 10 weeks (DIO-KO) and DIO mice treated with a NOX2 blocker, apocynin (DIO-Apocynin). Methods: Trans-esophageal rapid (TE) pacing was used to look at the AF phenotype. Cellular electrophysiology (EP), Western blotting, whole-cell patch clamping were performed to study ion channel remodeling and ROS production. Results: All three DIO mouse groups displayed significantly greater body weight compared to their respective controls (Figure A) After TE pacing, DIO-Apocynin mice displayed 28.26 ± 25.40 s and DIO-KO mice displayed 17.43 ± 31.80 s compared to 167.3 ± 168.9 s in DIO mice (Figure B). NOX2 inhibition reversed obesity-induced ion channel remodeling of potassium channels such as KCNQ1 and KCNE1 encoding for the IKs current and KCNA5 encoding for the IKur current and also reduced mediators of oxidative stress. (Figure C-M) Lastly, voltage clamp in DIO-KO mice showed that NOX2 inhibition reverses obesity-induced IK current increase. (Figure N-O) Conclusions: Thus, these results prove that antioxidant therapy targeting Nox2 abrogated ion channel remodeling and reversed the obesity-induced AF burden. Our findings show the importance of targeting specific antioxidant pathways to manage the AF in patients with obesity.